The molecular and cellular mechanisms underlying the repair of the skin tissue has not been sufficiently investigated yet. As a consequence, the failure of the skin tissue to heal is still poorly understood, and current therapies are quite limited. Improper wound healing after trauma, acute illness, surgical interventions, or chronic disease conditions affects millions of people worldwide each year and is the consequence of misregulated elements of the tissue repair program that occurs in healthy tissue response. The repair response is a complex process which includes inflammation, angiogenesis, deposition of extracellular matrix and cell recruitment. Notably, the failure of one or more of the above stated cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes or aging, which are all frequently associated with healing pathologies (Eming et al., 2014; Science Translational Medicine, (6), 265: 1-15).
The process of wound healing is a dynamic one, and involves complex and phase-dependent interactions between cells, extracellular matrix (ECM), ECM components such as growth factors that work together to reconstitute tissue following injury (Clark et al., 2007, 127(5): 1018-1029). The wound healing processes can be classified into the following four phases: the inflammatory or exudative phase (cleansing phase), the granulation phase, the epithelization phase, and the reparative phase. The epithelization phase and the reparative phase are occasionally considered as one. The challenge of a successful wound care treatment is to specifically address the different requirements of the above described healing phases.
Within wound care management the wound infection, the protease imbalance and the exudate management proved to be three key aspects which have to be addressed for promoting the wound healing.
Exudate Management
The generation of wound exudate occurs as a consequence of vasodilation that takes place during the early inflammatory phase of the wound healing as induced by inflammatory transmitters such as bradykinin and histamine. The wound exudate is a serous fluid contained within the wound bed and represents a part of normal wound healing process in acute wounds. However, as soon as the wound becomes a chronic non-healing wound with abnormal, persistent inflammation or with an established infection, the exudate plays a different role and will become a challenge in the wound care treatment. Notably, the wound exudate as generated in chronic wound contains components which are not observed in exudate from acute wounds such as proteolytic enzymes and other deleterious components. Hence, the chronic wound exudate has been regarded as ‘a wounding agent in its own right’ because it induces the degradation of growth factors and peri-wound skin tissue and makes the tissue vulnerable to further inflammation.
As a consequence of the above mentioned effects of wound exudate, an effective exudate management has now become a key strategy within the treatment of chronic exuding wounds. First products show that the exudate management allows to accelerate the healing process, reduces the exudate-related problems such as infection and maceration, reduces frequency for changing the wound dressings and ultimately improves healthcare efficiency in view of costs and increases quality of life for the patient.
Wound dressings represent the dominant option for managing the wound exudate within the wound site. An optimal dressing should combine two different, in some respect contradictory effects: The dressings should remove excessive wound exudate but in the same instance retain a certain wound moisture. Most of the dressing materials remove the wound exudate by absorption within the dressing or by allowing an exudate evaporation. The simplest absorptive materials exhibit void spaces within their structure for taking up the fluids. Examples are viscose cotton, or polyester fabrics and polymer foams e.g. made from silicone or polyurethane. Notably these “simple” absorbers are not able to retain the wound exudate under pressure. In contrast there are improved dressing materials, such as hydrocolloids, alginates, carboxymethylcellulose (CMC) fibers and especially superabsorbent polymers (SAP) which have the ability to absorb higher amounts of liquids and furthermore, by forming a hydrogel, to retain a high proportion of said absorbed exudate even under pressure. Notably, for strongly exuding wounds the combination of absorbing wounds dressing together with negative pressure has been observed to be beneficial.
Imbalance of Healing Promoting Factors
The chronification is caused by or associated with an imbalance of factors that enable a proper wound healing. For example an excess of matrix metalloproteases such as collagenase or gelatinase A or B degrade matrix components, such as fibronectin, as well as various key growth factors, all of which are required for cell growth and the remodelling of the extracellular matrix. Furthermore, it was found out that the addition of certain growth factors, chemokines or cytokines can accelerate the wound healing process such as epidermal growth factor (EGF), transforming growth factor-beta (TGF-β), or platelet-derived growth factor (PDGF).
NO as Multi-Effective Key Player
Furthermore the gas nitric oxide was found out to represent a key role in wound healing having several modes of actions such as antimicrobial properties, modulation of cytokine function, modulation of platelet function, vasodilatory effects, promotion of angiogenesis and matrix deposition. While first results of administering nitric oxide to skin wounds have shown substantial promise, the current modalities suffer from varying drawbacks, such as administration site irritation due to NO overdosing or the burden of large, expensive equipment.
Although there are wound care articles in the prior art which addresses some of the above discussed key aspects there is still no dressing that represents a proper combination of the different aspects such as wound exudate management and undisturbed release of bioactive agents, especially NO.
Hence, there is still a need for an improved wound care product that addresses the different complex requirements for an improved wound healing. The objective of the present invention thus is to provide a wound care product which overcomes at least one of the above mentioned disadvantages.
This problem is solved by provision of a wound care product Specific embodiments are described below.